Taniyama H, Hirayama K, Kagawa Y, Kurosawa T, Tajima M, Yoshino T, Furuoka H
Department of Veterinary Pathology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
J Vet Med Sci. 1999 Jul;61(7):803-10. doi: 10.1292/jvms.61.803.
Histological and immunohistochemical studies were carried out on the pancreas of twelve cattle of insulin-dependent diabetes mellitus (IDDM). They showed clinical signs such as persistent hyperglycemia, glycosuria and decreased glucose tolerance, and some cases accompanied with or without ketonuria. Histopathologically, eight cattle were diagnosed as chronic IDDM, while others were acute IDDM. The most characteristic lesions of the pancreas in chronic IDDM showed a decrease in the size and number of pancreatic islets, interlobular and interacinar fibrosis, mild lymphocytic insulitis, and vacuolation of a few islets. Almost all cells in the atrophied islets had a small amount of ungranulated cytoplasm. Immunohistochemical examination revealed that the atrophied islet cells did not react to anti-insulin antibody, but occasionally reacted to anti-glucagon or somatostatin antibodies. A few solitary islets with mild lymphocytic infiltration, necrotic islets with occasional calcification, and atrophied islets with mild fibrosis were also observed. A few islets consisted of many islet cells with vacuolated cytoplasm including a small number of insulin-positive granules. Accumulation of glycogen granules was occasionally observed in these islets. Islet fibrosis was due to the proliferation of collagen fibers reactive to both anti-collagen type I and type III antibodies. In acute IDDM, the major islets consisted of the cells with vacuolated cytoplasm indicating the degranulation of islet cells. These islets contained many islet cells with shrunken cytoplasm and karyorrhectic nuclei. Lymphocytic infiltration was frequently observed in the islets which consisted of many islet cells having karyorrhectic nuclei and vacuolated and severely degranulated cytoplasm. Immunohistochemically, islet cells with vacuolated cytoplasm had a small amount of insulin-positive granules, suggesting severe degranulation of beta-cells. An increase in acinar islet-cells and proliferation of ductal epithelial cells showing insulin-immunoreactivity were observed. Bovine IgG-immunoreactive islet cells were frequently seen in the vacuolated islets. In summary, pathological observations suggested that beta-cells were being destroyed by an inflammatory process which selectively affected the pancreatic islets. Lymphocytic insulitis and anti-bovine immunoreactive islet cells were thought to be the most significant changes in determining the etiology and pathogenesis of bovine IDDM, and suggested their role in anti-islet autoimmunity in this form of diabetes.
对12头胰岛素依赖型糖尿病(IDDM)牛的胰腺进行了组织学和免疫组织化学研究。它们表现出持续高血糖、糖尿和葡萄糖耐量降低等临床症状,部分病例伴有或不伴有酮尿。组织病理学上,8头牛被诊断为慢性IDDM,其他为急性IDDM。慢性IDDM胰腺最具特征性的病变表现为胰岛大小和数量减少、小叶间和腺泡间纤维化、轻度淋巴细胞性胰岛炎以及少数胰岛空泡化。萎缩胰岛中的几乎所有细胞都有少量无颗粒的细胞质。免疫组织化学检查显示,萎缩的胰岛细胞对抗胰岛素抗体无反应,但偶尔对抗胰高血糖素或生长抑素抗体有反应。还观察到少数有轻度淋巴细胞浸润的孤立胰岛、偶有钙化的坏死胰岛以及有轻度纤维化的萎缩胰岛。少数胰岛由许多细胞质空泡化的胰岛细胞组成,包括少量胰岛素阳性颗粒。这些胰岛中偶尔可见糖原颗粒积聚。胰岛纤维化是由于对I型和III型抗胶原抗体均有反应的胶原纤维增殖所致。在急性IDDM中,主要胰岛由细胞质空泡化的细胞组成,表明胰岛细胞脱颗粒。这些胰岛含有许多细胞质萎缩和核固缩的胰岛细胞。在由许多有核固缩、细胞质空泡化和严重脱颗粒的胰岛细胞组成的胰岛中经常观察到淋巴细胞浸润。免疫组织化学显示,细胞质空泡化的胰岛细胞有少量胰岛素阳性颗粒,提示β细胞严重脱颗粒。观察到腺泡胰岛细胞增多以及显示胰岛素免疫反应性的导管上皮细胞增殖。在空泡化的胰岛中经常见到牛IgG免疫反应性胰岛细胞。总之,病理观察表明β细胞正被一种选择性影响胰腺胰岛的炎症过程破坏。淋巴细胞性胰岛炎和抗牛免疫反应性胰岛细胞被认为是确定牛IDDM病因和发病机制的最显著变化,并提示它们在这种糖尿病形式的抗胰岛自身免疫中的作用。